Psilocybin (IPA: /saɪləˈsaɪbɪn/) (also known as psilocybine) is a psychedelicindole of the tryptamine family, found in psilocybin mushrooms. It is present in hundreds of species of fungi, including those of the genus Psilocybe, such as Psilocybe cubensis and Psilocybe semilanceata, but also reportedly isolated from a dozen or so other genera. Psilocybin mushrooms are commonly called "magic mushrooms" or more simply "shrooms".

Possession, and in some cases usage, of psilocybin or psilocin has been outlawed in most countries across the globe.[1]

The intensity and duration of entheogenic effects of psilocybin mushrooms are highly variable, depending on species/cultivar of mushrooms, dosage, individual physiology, and set and setting. Though psilocybin rarely attracts much attention from mainstream media, when it does the focus tends to be on the recreational use, generally excluding any other uses of the drug.

Albert Hofmann, the well-known chemist who discovered and experimented with LSD, was the first to recognize the importance and chemical structure of the pure compounds psilocybin and psilocin. Hofmann was aided in this process by his willingness to ingest extracts isolated from Psilocybe. Hofmann's colleagues at the University of Delaware were also trying to isolate the active principle, but were unsuccessful.[3]

Biology

Psilocybin is a naturally-occurring compound found in varying concentrations in some species of the genera of Psilocybe spp. and Panaeolus spp. (fungal Phylum Basidiomycota). The spores of these mushrooms are completely free of both psilocybin and psilocin. Mushroom caps tend to contain more of the psychoactive compounds than the stems.[4][5][6] The total potency varies greatly between species and even between specimens of one species in the same batch.[7] Younger, smaller mushrooms are relatively higher in alkaloids and have a milder taste than larger, mature mushrooms. Mature mycelium contains some psilocybin, while young mycelium (recently germinated from spores) does not contain appreciable amounts of alkaloids.[8] Many species of mushrooms containing psilocybin also contain small amounts of the psilocybin analogs baeocystin and norbaeocystin.[9][10][11] Most species of psilocybin-containing mushrooms bruise blue when handled or damaged[12] due to the oxidization of phenolic compounds. This is not a definitive method of identification or determining a mushroom's potency.

Two current studies are investigating the possibility that psilocybin can ease the psychological suffering associated with cancer. One study, led by Charles Grob, involves 12 subjects with terminal cancer being administered the hallucinogen or a placebo in two separate sessions.[16][17][18] A second study, led by Roland Griffiths at Johns Hopkins, will administer psilocybin on two occasions to people "with a current or past diagnosis of cancer who have some anxiety or are feeling down about their cancer".[19]

Toxicity

The toxicity of psilocybin is relatively low; in rats, the oral LD50 is 280mg/kg, approximately one and a half times that of caffeine. When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5mg/kg[20] (however rabbits are extremely intolerant to the effects of most psychoactive drugs). The lethal dose from psilocybin toxicity alone is unknown at recreational or medicinal levels, and has never been documented. Psilocybin makes up roughly 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms of dried mushrooms, or 17 kilograms of fresh mushrooms, would be required for a 60kg person to reach the 280mg/kg LD50 rate of rats.

Physiology

Psilocybin is absorbed through the lining of the mouth and stomach. Effects begin 10–40 minutes after ingestion of psilocybin-containing mushrooms, and last from 2–6 hours depending on dose, species, and individual metabolism.[21] A typical recreational dosage is from 10–50 mg psilocybin. However, a very small number of people are unusually sensitive to psilocybin's effects, where a normally threshold dose of around 2 mg of psilocybin can result in effects usually associated with medium and high doses. Likewise, there are some people who require relatively high doses of psilocybin to gain low-dose effects. Individual brain chemistry and metabolism plays a large role in determining a person's response to psilocybin.

Psilocybin is metabolized mostly in the liver where it becomes psilocin. It is broken down by the enzyme monoamine oxidase. MAO inhibitors have been known to sustain the effects of psilocybin for longer periods of time; people who are taking an MAOI for a medical condition or are seeking to potentiate the mushroom experience may experience highly potentiated effects.

Mental and physical tolerance to psilocybin builds and dissipates quickly. Taking psilocybin more than three or four times in a week (especially on consecutive days) can result in diminished effects. Tolerance dissipates after a few days, so frequent users often keep doses spaced five to seven days apart to avoid the effect.

Effects

The effects of psilocybin are highly variable, and dependent on the current mood and overall sense of well-being by the individual. Initially the subject may begin to feel somewhat disorientated, lethargic, and euphoric or sometimes depressed. At low doses, hallucinatory effects may occur, including enhancement of colors and the animation of geometric shapes. Closed-eye hallucination may occur, where the affected individual may see multi-coloured geometric shapes and vivid imaginative sequences. At higher doses, hallucinatory effects increase and experiences tend to be less social and more introspectic or entheogenic. Open-eye visuals are more common, and may be very detailed although rarely confused with reality.

Distortions in the experience of time in psilocybin-induced states have been subjectively reported [22], and objectively measured [23]. In these studies, psilocybin significantly decreased subjects’ reproduction of time intervals longer than 2.5 s, impaired their ability to synchronize to inter-beat intervals longer than 2 s, and reduced their preferred tapping rate. Recent studies into the effects of psilocybin on time interval reproduction may shed light on qualitative alterations of time experience in experimentally-induced altered states of consciousness, mystical states, or in psychopathology.[24]

Users having a pleasant experience can feel ecstatic, a sense of connection to others, nature, the universe, and other feelings/emotions are often intensified. Difficult experiences or bad trips occur due to a variety of reasons. Tripping during an emotional/physical low, or in a non-supportive/inadequate/etc. environment (see: set and setting) could possibly cause anxiety or some sort of freak-out. Latent psychological issues may be triggered by the strong emotional components of the experience. [25]

Some of these individuals report that they have experienced a 'spiritual' episode. For example, in the Marsh Chapel Experiment, which was run by a graduate student at Harvard Divinity School under the supervision of Timothy Leary, almost all of the graduate degree divinity student volunteers who received psilocybin reported profound religious experiences.

In 2006, a group of researchers from Johns Hopkins School of Medicine led by Roland R Griffiths conducted an experiment assessing the degree of mystical experience and attitudinal effects of the psilocybin experience; this report was published in the journal Psychopharmacology. Thirty-six volunteers without prior experience with hallucinogens were given psilocybin and methylphenidate (Ritalin) in separate sessions, the methylphenidate sessions serving as a control and psychoactive placebo; the tests were double-blind. The degree of mystical experience was measured using a questionnaire on mystical experience developed by Ralph W Hood; 61% of subjects reported a "complete mystical experience" after their psilocybin session, while only 13% reported such an outcome after their experience with methylphenidate. Two months after taking psilocybin, 79% of the participants reported moderately to greatly increased life satisfaction and sense of well-being. About 36% of participants also had a strong to extreme “experience of fear” or dysphoria (i.e., a “bad trip”) at some point during the psilocybin session (which was not reported by any subject during the methylphenidate session), with about one-third of these (13% of the total) reporting that this dysphoria dominated the entire session. These negative effects were reported to be easily managed by the researchers and did not have a lasting negative effect on the subject’s sense of well-being.[26] Further measures at 14 months after the psilocybin experience confirmed that participants continued to attribute deep personal meaning to the experience. This research was widely covered in the major media outlets.[27] The research team cautions that if hallucinogens are used in less well supervised settings, the possible fear or anxiety responses could lead to harmful behaviors.[28] Further studies by this group have investigated the relationship of psilocybin dose to likelihood of mystical experience in healthy volunteers[29] and whether mystical experiences in volunteers given psilocybin can help with anxiety and poor mood due to cancer.[30]

Possession and use of psilocybin mushrooms, including the bluing species of Psilocybe, is therefore prohibited by extension. However, in many national, state, and provincial drug laws, there is a great deal of ambiguity about the legal status of psilocybin mushrooms and the spores of these mushrooms, as well as a strong element of selective enforcement in some places. For more details on the legal status of psilocybin mushrooms and Psilocybe spores, see: Psilocybe: Social and legal aspects.

Because of the ease of cultivating psilocybin mushrooms or gathering wild species, purified psilocybin is often extremely difficult to find on the market.